1. Field of the Invention
This invention relates to novel chemical compounds and the preparation thereof, their use as therapeutic agents, and their formulation as pharmaceutical compositions. More particularly, this invention relates to novel 2-carboxy-5-oxo-5H-dibenzo[ a,d]cycloheptenes and the corresponding 10,11-dihydro compounds which are substituted at the 7,8 or 9 position with a halogen, hydroxy, lower alkyl, or lower alkoxy, and the pharmaceutically acceptable esters and salts thereof. The compounds are useful for the treatment of auto-immune diseases and allergic reactions when administered with suitable pharmaceutical excipients.
2. Prior Art
It is known that 5H-dibenzo[a,d]cycloheptenones are useful as precursors in the preparation of pharmacologically active compounds, and, in particular, they are useful in the preparation of compounds having tranquilizing, anti-depressant, analgesic, anti-inflammatory, psychotropic, anti-convulsants and anti-histaminic activity. See for example U.S. Pat. No. 3,551,498 to Tristrom et al of Merck; U.S. Pat. No. 3,256,335 to Slates et al of Merck; British 994,485 to Pfizer; U.S. Pat. No. 3,780,061 to Allais; British 1,076,612 to Merck; U.S. Pat. No. 3,803,234 to Dostert et al of Hoffman La Roche and Journal of Organic Chemistry, 27, 230-240, (1962), "New Psychotropic Agents Derivatives of Dibenzo [a,d]-1,4-cycloheptadiene" by Winthrop et al of Ayerst Research Labs.
In U.S. Pat. No. 3,780,061 the compound 5-oxo-8-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-3-carboxylic acid is disclosed as an intermediate for the preparation of the corresponding 3-acetic acid, an analgesic or anti-inflammatory. No therapeutic utility is given for this intermediate or for other intermediates in the other patents cited.
Surprisingly, we have now discovered that the specific 2-carboxy-5-oxo-5H-dibenzo[a,d]cycloheptene and the corresponding 10,11-dihydro compounds which are substituted at the 7, 8 or 9 position with halogen, hydroxy, lower alkyl, or lower alkoxy show therapeutic activity in the treatment of auto-immune diseases and allergic reactions. The compounds of this invention are undisclosed in the prior and the most closely related compound disclosed in U.S. Pat. No. 3,780,061 is not shown to have therapeutic activity.